2018 MEDICARE CODING UPDATE P. 19 • TORIC ALIGNMENT TECH P. 22 SUPPLEMENTS AND GLAUCOMA P. 40 • GORE-TEX SUTURING TRICKS P. 47 A REVIEW OF POSTERIOR SCLERITIS P. 50 • PEDIATRIC OCULAR ONCOLOGY P. 55 Review of Ophthalmology Vol. XXV, No. 2 • February 2018 • Presbyopic Corneal Inlays • Breakdown of Corneal • Breakdown Inlays 2018 • Presbyopic No. 2 • February Review of Ophthalmology Vol. XXV, FFebruaryebruary 22018018 reviewofophthalmology.comrreviiewofophthalmology.com NEW SCHOOL ANNUAL REFRACTIVE SURGERY ISSUESSUE Refractive Surgery OLD SCHOOL At A Crossroads New devices and procedures are emerging, but will they topple the tried-and-true? • Can Corneal Inlays Work forfor You?You? P. 26 • Breaking Down the SMILE ProcedureProcedure P. 3232 • Is There Still a Place for ManualManual LRIs?LRIs? P. 36 SMILE • • SMILE Manual LRIs • Toric Alignment Manual LRIs • Toric 001_rp0118_fc 2.indd 1 1/26/18 2:59 PM YOUR PATIENTS’ EYES TAKE IN A LOT. Sometimes it’s not all good. SYSTANE ® BALANCE Lubricant Eye Drops are scientifi cally formulated to work on all 3 layers of the tear fi lm, protecting the ocular surface with ingredients that increase lipid layer thickness by 40%.*,1 Recommend SYSTANE® BALANCE to your patients for the temporary relief of dry eye symptoms, and see how science leads to real relief. *Prospective, randomized, double-masked, single-dose, contralateral eye study, N=40. Lipid layer thickness was measured in nanometers, and baseline measurement was 63.38. The Relief is Real 1. Korb D, et al. Evaluation of extended tear stability by two emulsion based artifi cial tears. Poster presented at: 6th International Conference on the Tear Film and Ocular Surface: Basic Science and Clinical Relevance; September 22-25, 2010; Florence, Italy. © 2016 Novartis 12/16 US-SYS-16-E-5049 RP1017_Alcon Systane.indd 1 9/15/17 10:25 AM REVIEW NEWS Volume XXV • No. 2 • February 2018 Research Highlights from The Latest OIS Meeting Just before this year’s annual American says. “In the study, it was suggested the Graybug Vision implants should, Academy of Ophthalmology meeting, that a higher proportion of patients theoretically, inhibit all isoforms over ophthalmologists and industry leaders can go to a less-frequent, 12-week dos- six months or more.” got together at the Ophthalmology ing schedule.” • Opthea presented evidence of Innovation Summit to discuss the • The company PanOptica is also add-on or combination effi cacy with status of various nascent drugs, developing a topical AMD treatment, their anti-VEGF C/D TRAP-like devices and ophthalmic companies, a small-molecule tyrosine kinase in- mole cule. “Interestingly,” notes Dr. with an eye toward their current or hibitor that has shown an effect. “We Cunningham, “they showed that they future fi nancial performance. Review currently have very effective therapies could get regression of the neovascu- caught up with OIS co-chair Emmett in the form of intravitreal injections,” larization in half of the patients that T. Cunningham Jr, MD, PhD, MPH, Dr. Cunningham says, “so there is a were treated in the current study.” for his take on the highlights of the high threshold for effi cacy. This always • Iconic Therapeutics is work- ophthalmic pipeline. makes for a high hurdle for something ing on a tissue-factor inhibitor for In the retina realm, several products that’s not administered in the eye, but wet AMD, ICON-1, that has shown generated buzz: rather is delivered topically.” an ability to reduce retinal thickness • This fall, Spark Therapeutics’ • Genentech is continuing its LAD- and perhaps result in a more durable gene therapy for inherited blindness, DER trial for extended-release ranibi- effect when used in combination with Luxturna, received a unanimous vote zumab. “It involves a surgical proce- ranibizumab. “ICON-1 is an anti- for approval by the FDA review panel, dure to implant the device needed to tissue-factor fusion protein that has and followed this up with a Decem- achieve extended release,” Dr. Cun- a unique target,” Dr. Cunningham ber approval. “I think Spark’s Phase ningham explains. “The intention with explains. “They showed that, when it III data was, in a word, tremendous,” extended release is to decrease the was added to ranibizumab, there was Dr. Cunningham says. “This is the fi rst frequency of injections from monthly more drying than with ranibizumab gene therapy we’ve seen approved in to every three or four months, or even alone, though it was a small trial. The ophthalmology, and there’s a clear ef- less frequently. It will be interesting to vision didn’t change with the combina- fi cacy benefi t.” Dr. Cunningham notes see how much extended-release ability tion, however. I believe they plan to do that gene-therapy trials coming up be- LADDER shows.” a confi rmatory Phase II trial.” hind Luxturna include GenSight’s trial • The pharmaceutical company • Allegro is working on an anti- for Leber’s Congenital Optic Neurop- Graybug Vision has been studying its integrin inhibitor as a treatment for athy, AGTC’s trials in X-linked retinos- six-month, time-release delivery of the diabetic retinopathy that, according chisis and achromatopsia; Nightstar’s small molecule sunitinib for wet AMD to a post-hoc analysis of the Phase II trial for choroideremia; and Regenx- in animal models. Dr. Cunningham, data, may have enhanced effi cacy in bio’s trial in wet AMD. who is an investor in Graybug, says patients who are incomplete respond- • Novartis’ brolucizumab, a small, that, if the approach works, it could ers to anti-VEGF drugs. “There ap- single-chain variable antibody frag- be a broad inhibitor of the factors that pears to be a clear drug effect.” Dr. ment, was shown to be noninferior to promote AMD. “The current anti- Cunningham says. “You can see some afl ibercept (Eylea, Regeneron), for the VEGF agents are all targeting VEGF drying. And, as monotherapy, it seems treatment of wet age-related macular isoform A,” Dr. Cunningham explains. to be an improvement vs. anti-VEGF. degeneration. “So, it looks like we’ll “But there are other isoforms—par- However, now they’re trying to fi gure have a fourth competitor coming to ticularly C and D—that also appear the way forward: Do they treat non- the AMD market,” Dr. Cunningham to be important. The sunitinib that responders? All patients? They haven’t (Continued on p. 8) February 2018 | reviewofophthalmology.com | 3 0003_rp0218_news.indd03_rp0218_news.indd 3 11/26/18/26/18 22:55:55 PPMM Ophthalmic Product Development Insights Aki Tobaru, Hiro Matsuda, PhD, & Matthew Chapin • Ora Inc., Andover, Mass. REVIEW Matthew Chapin and Hal Patterson • Andover, Mass. Nonclinical Considerations: Focus on Chemistry, Manufacturing and Controls n this installment of Ophthalmic Product approaches to container closure: multi- formulation for GLP ocular toxicology that’s Development Insights, we’ll review dose, three-part systems (bottle, tip, cap); similar to—or, optimally, the same as—that Iconsiderations for early-stage develop- blow-fi ll seal (BFS; typically unit dose and used in your intended clinical study. In many ment of a new product as the entrepreneur preservative-free); and tubes, which are cases, formulation and scale-up are the charts his path to the fi rst clinical trial. Most generally used for ointments. Other novel rate-limiting factors in ophthalmic product of the prior columns have emphasized that systems like multidose, preservative-free development, so setting your formulation having the target-product profi le drafted bottles; or dual-chamber containers that early and then locking it in for the trials is and defi ned early is critical to under- allow drug components to be separate until important. standing key elements that contribute to mixing before use, are available for consid- If changes to the formulation are neces- designing a proper clinical development eration but are more complex solutions that sary as you proceed through your nonclinical strategy. In this article, we’ll specifi cally often aren’t used in early trials due to their program, you need to consider whether look at issues around CMC (Chemistry, time and cost requirements, which can be you can demonstrate to the FDA that those Manufacturing and Controls), an area that’s prohibitive for startup companies. In those changes don’t impact safety or penetration often outside the expertise and experience cases, alternatives for use in the early trials of the drug into the ocular tissues. Adding a should be considered. In some situations of the entrepreneur ophthalmologist. Proper demulcent, for example, while a seemingly benign addition, can increase dwell time of CMC planning requires a basic understand- the drug on the surface of the eye and ing of the various interdependent thus, theoretically, drug penetra- steps of development: the design tion. Don’t underestimate the of the fi rst clinical trial and implications of formulation of the toxicology studies; a changes as you near investi- preliminary idea of the com- gational new drug status with mercial container closure; the FDA. It goes without saying formulations; clinical dosing; that you want to avoid having to pharmacokinetic consider- repeat GLP ocular toxicology. ations; and other components. Another aspect of formulation you All of these factors infl uence the don’t want to underestimate is the CMC strategy. addition of the preservative, which is We aren’t able to exhaustively review usually required for multidose containers. all of the critical requirements for CMC here, While, again, simply adding a preservative but we can offer a few pearls we’ve picked in which a unit-dose blow-fi ll seal doesn’t may be considered a benign change, it’s the up after taking part in many development fi t the timeframe/cost of the early program, type of change that requires a confi rmation projects.